The evolutionary landscape of colorectal tumorigenesis.
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Cross W
Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Kovac M
Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Mustonen V
Organismal and Evolutionary Biology Research Programme, Department of Computer Science, Institute of Biotechnology, Helsinki Institute for Information Technology HIIT, University of Helsinki, Helsinki, Finland.
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Temko D
Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Davis H
Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Baker AM
Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Biswas S
Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Arnold R
Cancer Bioinfomatics Group, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
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Chegwidden L
Gastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
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Gatenbee C
Integrated Mathematical Oncology Department, Moffitt Comprehensive Cancer Centre, Tampa, FL, USA.
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Anderson AR
Integrated Mathematical Oncology Department, Moffitt Comprehensive Cancer Centre, Tampa, FL, USA.
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Koelzer VH
Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Martinez P
Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Jiang X
Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
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Domingo E
Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Woodcock DJ
Big Data Institute, University of Oxford, Oxford, UK.
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Feng Y
Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Kovacova M
Institute of Mathematics and Physics, Faculty of Mechanical Engineering, Slovak University of Technology in Bratislava, Bratislava, Slovakia.
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Maughan T
Department of Oncology, University of Oxford, Oxford, UK.
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Jansen M
Department of Research Pathology, Cancer Institute, University College London, London, UK.
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Rodriguez-Justo M
Department of Surgery, University Hospitals Birmingham, Birmingham, UK.
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Ashraf S
Department of Colorectal Surgery, Cancer Centre, Churchill Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
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Guy R
Department of Colorectal Surgery, Cancer Centre, Churchill Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
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Cunningham C
Translational Gastroenterology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK.
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East JE
Big Data Institute, University of Oxford, Oxford, UK.
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Wedge DC
Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Wang LM
Gastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
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Palles C
Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
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Heinimann K
Evolutionary Genomics and Modelling Lab, Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
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Sottoriva A
Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Leedham SJ
Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. t.graham@qmul.ac.uk.
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Graham TA
Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. i.tomlinson@bham.ac.uk.
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Tomlinson IPM
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Published in:
- Nature ecology & evolution. - 2018
English
The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome and exome sequencing of 24 benign and malignant colorectal tumours, we investigate the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations-considered to be functionally important in the carcinogenic process-that have not swept to fixation, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas by widespread aneusomies that are usually clonal and often accrue in a 'punctuated' fashion. We conclude that adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilizing selection.
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green
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https://sonar.ch/global/documents/232370
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